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The Lancet. Global Health Aug 2022Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with...
BACKGROUND
Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival.
METHODS
We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models.
FINDINGS
The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0-36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8-100·0) for children from high-income countries, 91·2% (89·5-93·0) for children from upper-middle-income countries, 80·3% (78·3-82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76-50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44-18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23-1·56). For children aged 3-7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope).
INTERPRETATION
This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.
FUNDING
Queen Elizabeth Diamond Jubilee Trust.
Topics: Child; Eye Enucleation; Humans; Infant; Prospective Studies; Retinal Neoplasms; Retinoblastoma; Treatment Outcome
PubMed: 35839812
DOI: 10.1016/S2214-109X(22)00250-9 -
Pediatric Clinics of North America Feb 2015Retinoblastoma is the most common neoplasm of the eye in childhood, and represents 3% of all childhood malignancies. Retinoblastoma is a cancer of the very young;... (Review)
Review
Retinoblastoma is the most common neoplasm of the eye in childhood, and represents 3% of all childhood malignancies. Retinoblastoma is a cancer of the very young; two-thirds are diagnosed before 2 years of age and 95% before 5 years. Retinoblastoma presents in 2 distinct clinical forms: (1) a bilateral or multifocal, heritable form (25% of all cases), characterized by the presence of germline mutations of the RB1 gene; and (2) a unilateral or unifocal form (75% of all cases), 90% of which are nonhereditary. The treatment of retinoblastoma is multidisciplinary and is designed primarily to save life and preserve vision.
Topics: Genes, Retinoblastoma; Humans; Mutation; Neoplasm Staging; Retinal Neoplasms; Retinoblastoma
PubMed: 25435120
DOI: 10.1016/j.pcl.2014.09.014 -
Clinics in Perinatology Mar 2021Retinoblastoma is the most common ocular malignancy of childhood. With an estimated 300 cases annually in the United States, retinoblastoma is nevertheless considered a... (Review)
Review
Retinoblastoma is the most common ocular malignancy of childhood. With an estimated 300 cases annually in the United States, retinoblastoma is nevertheless considered a rare tumor. Although retinoblastoma primarily affects younger children, diagnosis during the neonatal age range is less common. However, an understanding of patients at risk is critical for appropriate screening. Early detection and treatment by a multidisciplinary specialty team maximizes the chance for survival and ocular/vision salvage while minimizing treatment-related toxicity. Testing for alterations in the RB1 gene has become standard practice, and informs screening and genetic counseling recommendations for patients and their families.
Topics: Child; Early Diagnosis; Genetic Counseling; Humans; Infant, Newborn; Mass Screening; Retinal Neoplasms; Retinoblastoma
PubMed: 33583507
DOI: 10.1016/j.clp.2020.12.001 -
The New England Journal of Medicine Apr 2024
Review
Topics: Humans; Retinal Neoplasms; Retinoblastoma
PubMed: 38631004
DOI: 10.1056/NEJMra1803083 -
Journal of Child Neurology Feb 2016Retinoblastoma is the most common primary intraocular malignancy of childhood. It typically presents with leukocoria or strabismus. In later stages of the disease, the... (Review)
Review
Retinoblastoma is the most common primary intraocular malignancy of childhood. It typically presents with leukocoria or strabismus. In later stages of the disease, the child may exhibit proptosis, buphthalmos, or hypopyon. The pathognomonic molecular aberration is a loss of function mutation in the RB1 gene on chromosome 13q. The degree of tumor involvement within the eye is defined by its group. Grouping was historically done with Reese-Ellsworth System. Recent therapeutic advances have led to the development of a new grouping system, the International Classification of Retinoblastoma (ICRB). In cases of extraocular extension and metastatic disease, the degree of tumor involvement outside of the eye is defined by its stage. Retinoblastoma is staged using the International Retinoblastoma Staging System (IRSS). Children with intraocular retinoblastoma have an excellent overall and ocular survival. In order to avoid the morbidity of enucleation and external beam radiation, treatments for isolated intraocular retinoblastoma have progressively moved toward targeted local modalities. Patients with extraocular involvement, such as those with trilateral retinoblastoma, have a poorer prognosis. The majority of these higher stage patients are now able to be cured with combination chemotherapy.
Topics: Child; Humans; Retinal Neoplasms; Retinoblastoma
PubMed: 26023180
DOI: 10.1177/0883073815587943 -
Functional & Integrative Genomics Dec 2022Retinoblastoma (RB), the most common malignant retinal tumor among children under 3 years old, is lethal if left untreated. Early diagnosis, together with timely and... (Review)
Review
Retinoblastoma (RB), the most common malignant retinal tumor among children under 3 years old, is lethal if left untreated. Early diagnosis, together with timely and effective treatment, is important to improve retinoblastoma-related outcomes. Circular RNAs (circRNAs), a new class of non-coding RNAs with the capacity to regulate cellular activities, have great potential in retinoblastoma diagnosis and treatment. Recent studies have identified circular RNAs that regulate multiple cellular processes involved in retinoblastoma, including cell viability, proliferation, apoptosis, autophagy, migration, and invasion. Six circular RNAs (circ-FAM158A, circ-DHDDS, circ-E2F3, circ-TRHDE, circ-E2F5, and circ-RNF20) promote disease progression and metastasis in retinoblastoma and function as oncogenic factors. Other circular RNAs, such as circ-TET1, circ-SHPRH, circ-MKLN1, and circ-CUL2, play tumor suppressive roles in retinoblastoma. At present, the studies on the regulatory mechanism of circular RNAs in retinoblastoma are not very clear. The purpose of this review is to summarize recent studies on the functional roles and molecular mechanisms of circular RNAs in retinoblastoma and highlight novel strategies for retinoblastoma diagnosis, prognosis, and treatment.
Topics: Child; Child, Preschool; Humans; Apoptosis; Cell Line, Tumor; Cell Proliferation; MicroRNAs; Retinal Neoplasms; Retinoblastoma; RNA, Circular
PubMed: 36547723
DOI: 10.1007/s10142-022-00942-9 -
Asia-Pacific Journal of Ophthalmology... 2018Retinoblastoma can present in 1 or both eyes and is the most common intraocular malignancy in childhood. It is typically initiated by biallelic mutation of the RB1 tumor... (Review)
Review
Retinoblastoma can present in 1 or both eyes and is the most common intraocular malignancy in childhood. It is typically initiated by biallelic mutation of the RB1 tumor suppressor gene, leading to malignant transformation of primitive retinal cells. The most common presentation is leukocoria, followed by strabismus. Heritable retinoblastoma accounts for 45% of all cases, with 80% being bilateral. Treatment and prognosis of retinoblastoma is dictated by the disease stage at initial presentation. The 8th Edition American Joint Committee on Cancer (AJCC) TNMH (tumor, node, metastasis, heritable trait) staging system defines evidence-based clinical and pathological staging for overall prognosis for eye(s) and child. Multiple treatment options are available in 2018 for retinoblastoma management with a multidisciplinary team, including pediatric ocular oncology, medical oncology, radiation oncology, genetics, nursing, and social work. Survival exceeds 95% when disease is diagnosed early and treated in centers specializing in retinoblastoma. However, survival rates are less than 50% with extraocular tumor dissemination. We summarize the epidemiology, genetics, prenatal screening, diagnosis, classification, investigations, and current therapeutic options in the management of retinoblastoma.
Topics: Child; DNA, Neoplasm; Genes, Retinoblastoma; Genetic Testing; Humans; Mutation; Ophthalmologists; Retinal Neoplasms; Retinoblastoma
PubMed: 29737052
DOI: 10.22608/APO.201870 -
Oncogene Mar 2018Retinoblastoma (Rb) is the most common primary intraocular malignancy of childhood, but an uncommon paediatric cancer, with a constant incidence worldwide of... (Review)
Review
Retinoblastoma (Rb) is the most common primary intraocular malignancy of childhood, but an uncommon paediatric cancer, with a constant incidence worldwide of 1:15,000-1:20,000 live births. Despite its rarity, Rb has served as a cornerstone in the field of oncology in many of the aspects that comprise cancer management, including classification schemes, treatment modalities, genetic testing and screening. Until just over half a century ago, the major treatment for Rb was eye removal, and prognosis was poor with outcome fatal for most children. The dramatic evolution, in a short period of time across all fields of Rb management, as well as the development of specialized centres, better infrastructure and introduction of awareness campaigns, has resulted in nearly 100% survival in developed countries and allowed eye salvage in many of the cases. External beam radiotherapy was used as the main treatment choice for four decades, but replaced by chemotherapy at the turn of the century. Initially, and still in many centres, chemotherapy is administered intravenously, but recently is targeted directly into the eye by means of intra-ophthalmic artery and intravitreal chemotherapy. To date, a range of treatments is available to the Rb expert, including enucleation, but there is lack of consensus in a number of scenarios as to what to use and when. In such a rare cancer, treatment outcomes are reported usually via retrospective analyses, with few prospective randomized controlled trials. Classification schemes have also evolved following the introduction of new treatment modalities, but discrepancies exist among centres with respect to the preferred schema and its interpretation. Retinoblastoma management is a remarkable success story, but the future will require a collaborative effort in the form of multicentre randomized controlled trials in order to further improve the quality of care for this subset of young children with ocular cancer.
Topics: Child; Eye Enucleation; Humans; Incidence; Organ Sparing Treatments; Prognosis; Retinal Neoplasms; Retinoblastoma; Treatment Outcome
PubMed: 29321667
DOI: 10.1038/s41388-017-0050-x -
NeoReviews Jul 2021Retinoblastoma (Rb) is the most common pediatric ocular malignancy and accounts for 2% of all childhood cancers. Rb is initiated by a mutation of the 1 tumor suppressor... (Review)
Review
Retinoblastoma (Rb) is the most common pediatric ocular malignancy and accounts for 2% of all childhood cancers. Rb is initiated by a mutation of the 1 tumor suppressor gene and occurs in 2 forms: 1) unilateral and unifocal, characterized by a single tumor in 1 eye, and 2) bilateral or unilateral, multifocal Rb with multiple tumor foci in 1 or both eyes. Rb is a disease of young children and if left untreated can result in visual morbidity as well as systemic mortality. Fortunately, because of the greater availability of genetic testing and earlier diagnosis, novel targeted therapies, and multimodal treatment approaches, disease-free survival rates and visual prognoses have improved dramatically. Current efforts to expand the accessibility of the newest Rb treatments aim to improve Rb outcomes worldwide. In this article, we will review the clinical presentation, diagnosis, and management of Rb, with a focus on the newest treatment approaches.
Topics: Child; Child, Preschool; Exons; Genetic Testing; Humans; Mutation; Retinal Neoplasms; Retinoblastoma
PubMed: 34210807
DOI: 10.1542/neo.22-7-e423 -
AJNR. American Journal of Neuroradiology Apr 2021Retinoblastoma is the most common primary intraocular tumor of childhood. Accurate diagnosis at an early stage is important to maximize patient survival, globe salvage,... (Review)
Review
Retinoblastoma is the most common primary intraocular tumor of childhood. Accurate diagnosis at an early stage is important to maximize patient survival, globe salvage, and visual acuity. Management of retinoblastoma is individualized based on the presenting clinical and imaging features of the tumor, and a multidisciplinary team is required to optimize patient outcomes. The neuroradiologist is a key member of the retinoblastoma care team and should be familiar with characteristic diagnostic and prognostic imaging features of this disease. Furthermore, with the adoption of intra-arterial chemotherapy as a standard of care option for globe salvage therapy in many centers, the interventional neuroradiologist may play an active role in retinoblastoma treatment. In this review, we discuss the clinical presentation of retinoblastoma, ophthalmic imaging modalities, neuroradiology imaging features, and current treatment options.
Topics: Humans; Infusions, Intra-Arterial; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Salvage Therapy
PubMed: 33509920
DOI: 10.3174/ajnr.A6949